Immunomodulatory Agents

Question 1

BCG

Answer 1

Immunostumulant: adjuvant
=live attenuated bacillus calmotte-guirin
Increases Ag Presenting Cell (APC) activity by directly stimulating their pattern recognition receptors.
Treat certain cancers

Question 2

IL2

Answer 2

Immunostimulant: cytokine
Increases proliferation of activated Tcells, Increases production of IFN-gamma, Increases cytotoxic killer activity 
Treat certain cancers 
treatment can be fatal
lacks specificity

Question 3

IFN-gamma

Answer 3

Immunostimulant: cytokine

Stimulate cell mediated cytotoxic immune response –> treat severe recurrent infection

Question 4

cyclophosphamide

Answer 4

Immunosuppressant
General Inhibitor of Cell Growth, Prevent Clonal Expansion
Cross-link DNA

Question 5

azathioprine

Answer 5

Immunosuppressant
General Inhibitor of Cell Growth, Prevent Clonal Expansion
Metabolized to 6-mercaptopurine –>6-thioguanine which incorporates into DNA as guanine, inhibits purine sythesis
Inactivated by xanthine oxidase
Decrease the dose when allolpurinol is given (allolpurinol inhibits xanthine oxidase)

Question 6

mycophenolate mofeitil

Answer 6

Immunosuppressant
General Inhibitor of Cell Growth, Prevent Clonal Expansion
Inhibits iosine monophosphatate dehydrogenase –> prevent purine synthesis

Question 7

methotrexate

Answer 7

Inhibits DHFR (dihydrofolate reductase) --> prevent synthesis of thymidein and purines
Drug of choise for Rhumatoid arthritis

Question 8

leflunomide

Answer 8

Immunosuppressant
General Inhibitor of Cell Growth, Prevent Clonal Expansion
Inhigibts dihyroorate dehydrogenase –> decrease pyrimidine synthesis

Question 9

prednisone

Answer 9

Immunosuppressant and AntiInflammatory: Glucocorticosteroid
Repress IL2, IFN-gamma
First line for solid organ and hematopoeitic stem cell transplant
Adverse with chronic use: Cushing’s Syndrome, glucose intolerance, osteoporosis, psych,… No marrow tox

Question 10

cyclosporin

Answer 10

Immunosuppressant: T cell Receptor Signalling Path Targeting
Forms complex with cyclophillin which inhibits calcineurin which dephosphorylates (activates) the transcription factor for cytokines like IL2, IFN-gamma…

Question 11

tacrolimus

Answer 11

Immunosuppressant: T cell Receptor Signalling Path Targeting
Forms complex with an immunophillin that inhibits calcineurin which dephosphorylates (activates) the transcription factor for cytokines like IL2, IFN-gamma…
10-100X more potent than cyclosporin

Question 12

sirolimus

Answer 12

Immunosuppressant 
Antagonize mTOR (mammalian target of rapamyacin) which regulates mRNA expression for IL2 (IL2 promotes clonal expansion)

Question 13

tacrolimus

Answer 13

Immunosuppressant: T cell Receptor Signalling Path Targeting
Forms complex with an immunophillin (FKBP12) that inhibits calcineurin which dephosphorylates (activates) the transcription factor for cytokines like IL2, IFN-gamma…
10-100X more potent than cyclosporin

Question 14

Rh (D) immuno globulin

Answer 14

Immunosupressant: Ag specific Immune Suppression Antibody

For preventing Rh Hemolytic Disease in moms with Rh+ babies

Question 15

belatacept

Answer 15

Immunosuppressant: Fusion protein (longer half life)
High affinity B7 ligand with IgGFc domain
Prevents interaction between B7 and CD28 –> prevent costimulation cause Tcells to become anergic

Question 16

ATG

Answer 16

Immunosuppresant: Anti-T cell Globulin
Block T cell surface receptors and opsonize T cells
Adverse: cytokine release syndrome (fever, chills, headache, nausea…)
Can be reduced via pretreat with acetaminophen and antihistamine
Serum sickness, anaphylaxis possible
Prolonged Tcell depletion possible which is why its used at the time of transplant and not much longer

Question 17

alemtuzumab

Answer 17

Immunosuppressant: anti-CD52 humanized antibody
(CD52 is a surface protein on T and B cells, monocytes, macrophages, NKcells)
Adverse myelosuppression, prolonged T cell depletion

Question 18

basiliximab

Answer 18

Immunosuppressant: humanized Ab
Depletes Ag activated T cells by opsonizing alpha-chain of IL2 receptor that is present on activated T cells
so can generate adaptive immunity
Well tolerated